Progress in the Use of HPLC for Evaluation of Lipophilicity

Abstract

Modern methods of organic synthesis allow an exponential increase in the number of compounds for screening as drug candidates, often as multicomponent mixture. That requires procedures for assessing lipophilicity parameters that are rapid and can be employed with very small samples. Especially suitable appear to be the methods providing the data needed without prior isolation of an individual component of a mixture. Chromatographic and electrochromatographic techniques are unique with that respect. This review will assess how is the progress in the chromatographic determination of lipophilicity parameters, which could be interesting from the point of view of search for new drugs. In the first paragraph the correlations between measures of lipophilicity from RP HPLC and the n-octanol-water partition coefficient are discussed. Then modern HPLC stationary phases employed in lipophilicity determination are briefly presented. The further paragraphs present the base of gradient HPLC technique employed in lipophilicity evaluation and the very recent results of correlation studies between chromatographic lipophilicity parameters and drug bioactivity data. Finally, the recent applications of electrochromatographic methods in assessment of lipophilicity of xenobiotics are described.